Re: human-human variation grows!

On Nov 4, 1:13 pm, "Perplexed in Peoria" <jimmene...@xxxxxxxxxxxxx>
wrote:
"Friar Broccoli" <Elia...@xxxxxxxxx> wrote in messagenews:1194187167.267727.297090@xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx
On Nov 4, 12:12 am, spintronic <spintro...@xxxxxxxxxxx> wrote:
http://www.jcvi.org/press/news/news_2007_09_03.php

"The new estimate based on this data is that genomes between
individuals have at least 0.5% total genetic variation (or are 99.5%
similar) The researchers suggest that much more research needs to be
done on these non-SNP variants to better understand their role in
individual genomics."

It goes from around 98% similar to 95%.

In phylogenetic analysis you don't want to deal with insertion/
deletions. You can't accurately handle them in the analysis. Just
look at this current example. You more than triple the number of
nucleotide differences, but the number of mutational events isn't
really sigificantly different. In the old days when we had to
struggle to sequence one gene, the last thing that you wanted to deal
with was indels. If you are missing 3 base-pairs from a certain
region of a gene should you count that as 1 event (likely) or 3 events
(not so likely)? When you are already dealing with minimal sequence
differences it makes a big difference sometimes. One way to deal with
it is just to take that region of the gene out of the analysis.

The most bang for your buck in terms of accurate phylogentic data is
to use SNPs (single nucleotide polymorphisms) and forget the indels.
When the first genomic deletion paper came out several years ago
demonstrating a much larger difference in total sequence between
chimps and humans, most old hands just shrugged. Absolutely no one
that wanted to do an accurate analysis of the difference in sequence
would count the differences the way that they are being counted to
make the new data seem like something interesting. In terms of
biological evolution you want to know the number of mutational
events. One event can delete or duplicate hundreds of thousands of
base-pairs.

The only interest they hold is that they could do major things in
terms of phenotypes. Just think around 1 in 300 people walking around
have a chromosomal abnormality that is big enough to see with a light
microscope. You might be changing the position of 1 or 2 percent of
the genome in a single event. We look at the difference between
chimps and humans and we see things like the chromosome 2 fusion event
along with 10 visible inversion events. The second largest chromosome
that humans have was created with a single fusion event. Does that
make the difference between chimps and humans 91% different instead of
95% different? In the end it was only a single event. It may have
been very important to the evolution of humans, but it only counts the
same as one single nucleotide mutation. Well that might not be quite
right because to get the fusion to work one centromere had to be
inactivated by a second mutation, so I guess you have to count it as
two mutations. Counting differences in the fashion that these indel
papers count it is just hype. No one wanting to do the science
correctly would count them that way.

Ron Okimoto

.

Relevant Pages

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